37 research outputs found
Discrete solution of the electrokinetic equations
We present a robust scheme for solving the electrokinetic equations. This
goal is achieved by combining the lattice-Boltzmann method (LB) with a discrete
solution of the convection-diffusion equation for the different charged and
neutral species that compose the fluid. The method is based on identifying the
elementary fluxes between nodes, which ensures the absence of spurious fluxes
in equilibrium. We show how the model is suitable to study electro-osmotic
flows. As an illustration, we show that, by introducing appropriate dynamic
rules in the presence of solid interfaces, we can compute the sedimentation
velocity (and hence the sedimentation potential) of a charged sphere. Our
approach does not assume linearization of the Poisson-Boltzmann equation and
allows us for a wide variation of the Peclet number.Comment: 24 pages, 7 figure
Quantifying the entropic cost of cellular growth control
We quantify the amount of regulation required to control growth in living
cells by a Maximum Entropy approach to the space of underlying metabolic states
described by genome-scale models. Results obtained for E. coli and human cells
are consistent with experiments and point to different regulatory strategies by
which growth can be fostered or repressed. Moreover we explicitly connect the
`inverse temperature' that controls MaxEnt distributions to the growth
dynamics, showing that the initial size of a colony may be crucial in
determining how an exponentially growing population organizes the phenotypic
space.Comment: 3 page
Quantitative constraint-based computational model of tumor-to-stroma coupling via lactate shuttle
Cancer cells utilize large amounts of ATP to sustain growth, relying primarily on non-oxidative,
fermentative pathways for its production. In many types of cancers this leads, even in the presence
of oxygen, to the secretion of carbon equivalents (usually in the form of lactate) in the cellâs
surroundings, a feature known as the Warburg effect. While the molecular basis of this phenomenon
are still to be elucidated, it is clear that the spilling of energy resources contributes to creating a
peculiar microenvironment for tumors, possibly characterized by a degree of toxicity. This suggests
that mechanisms for recycling the fermentation products (e.g. a lactate shuttle) may be active,
effectively inducing a mutually beneficial metabolic coupling between aberrant and non-aberrant
cells. Here we analyze this scenario through a large-scale in silico metabolic model of interacting
human cells. By going beyond the cell-autonomous description, we show that elementary physico-
chemical constraints indeed favor the establishment of such a coupling under very broad conditions.
The characterization we obtained by tuning the aberrant cellâs demand for ATP, amino-acids and
fatty acids and/or the imbalance in nutrient partitioning provides quantitative support to the idea
that synergistic multi-cell effects play a central role in cancer sustainmen
Modeling Networks of Coupled Enzymatic Reactions Using the Total Quasi-Steady State Approximation
In metabolic networks, metabolites are usually present in great excess over the enzymes that catalyze their interconversion, and describing the rates of these reactions by using the MichaelisâMenten rate law is perfectly valid. This rate law assumes that the concentration of enzymeâsubstrate complex (C) is much less than the free substrate concentration (S (0)). However, in protein interaction networks, the enzymes and substrates are all proteins in comparable concentrations, and neglecting C with respect to S (0) is not valid. Borghans, DeBoer, and Segel developed an alternative description of enzyme kinetics that is valid when C is comparable to S (0). We extend this description, which Borghans et al. call the total quasi-steady state approximation, to networks of coupled enzymatic reactions. First, we analyze an isolated GoldbeterâKoshland switch when enzymes and substrates are present in comparable concentrations. Then, on the basis of a real example of the molecular network governing cell cycle progression, we couple two and three GoldbeterâKoshland switches together to study the effects of feedback in networks of protein kinases and phosphatases. Our analysis shows that the total quasi-steady state approximation provides an excellent kinetic formalism for protein interaction networks, because (1) it unveils the modular structure of the enzymatic reactions, (2) it suggests a simple algorithm to formulate correct kinetic equations, and (3) contrary to classical MichaelisâMenten kinetics, it succeeds in faithfully reproducing the dynamics of the network both qualitatively and quantitatively
The Brain on Low Power Architectures - Efficient Simulation of Cortical Slow Waves and Asynchronous States
Efficient brain simulation is a scientific grand challenge, a
parallel/distributed coding challenge and a source of requirements and
suggestions for future computing architectures. Indeed, the human brain
includes about 10^15 synapses and 10^11 neurons activated at a mean rate of
several Hz. Full brain simulation poses Exascale challenges even if simulated
at the highest abstraction level. The WaveScalES experiment in the Human Brain
Project (HBP) has the goal of matching experimental measures and simulations of
slow waves during deep-sleep and anesthesia and the transition to other brain
states. The focus is the development of dedicated large-scale
parallel/distributed simulation technologies. The ExaNeSt project designs an
ARM-based, low-power HPC architecture scalable to million of cores, developing
a dedicated scalable interconnect system, and SWA/AW simulations are included
among the driving benchmarks. At the joint between both projects is the INFN
proprietary Distributed and Plastic Spiking Neural Networks (DPSNN) simulation
engine. DPSNN can be configured to stress either the networking or the
computation features available on the execution platforms. The simulation
stresses the networking component when the neural net - composed by a
relatively low number of neurons, each one projecting thousands of synapses -
is distributed over a large number of hardware cores. When growing the number
of neurons per core, the computation starts to be the dominating component for
short range connections. This paper reports about preliminary performance
results obtained on an ARM-based HPC prototype developed in the framework of
the ExaNeSt project. Furthermore, a comparison is given of instantaneous power,
total energy consumption, execution time and energetic cost per synaptic event
of SWA/AW DPSNN simulations when executed on either ARM- or Intel-based server
platforms
Quantitative analysis reveals how EGFR activation and downregulation are coupled in normal but not in cancer cells
Ubiquitination of the epidermal growth factor receptor (EGFR) that occurs when Cbl and Grb2 bind to three phosphotyrosine residues (pY1045, pY1068 and pY1086) on the receptor displays a sharp threshold effect as a function of EGF concentration. Here we use a simple modelling approach together with experiments to show that the establishment of the threshold requires both the multiplicity of binding sites and cooperative binding of Cbl and Grb2 to the EGFR. While the threshold is remarkably robust, a more sophisticated model predicted that it could be modulated as a function of EGFR levels on the cell surface. We confirmed experimentally that the system has evolved to perform optimally at physiological levels of EGFR. As a consequence, this system displays an intrinsic weakness that causesâat the supraphysiological levels of receptor and/or ligand associated with cancerâuncoupling of the mechanisms leading to signalling through phosphorylation and attenuation through ubiquitination
Gaussian and exponential lateral connectivity on distributed spiking neural network simulation
We measured the impact of long-range exponentially decaying intra-areal
lateral connectivity on the scaling and memory occupation of a distributed
spiking neural network simulator compared to that of short-range Gaussian
decays. While previous studies adopted short-range connectivity, recent
experimental neurosciences studies are pointing out the role of longer-range
intra-areal connectivity with implications on neural simulation platforms.
Two-dimensional grids of cortical columns composed by up to 11 M point-like
spiking neurons with spike frequency adaption were connected by up to 30 G
synapses using short- and long-range connectivity models. The MPI processes
composing the distributed simulator were run on up to 1024 hardware cores,
hosted on a 64 nodes server platform. The hardware platform was a cluster of
IBM NX360 M5 16-core compute nodes, each one containing two Intel Xeon Haswell
8-core E5-2630 v3 processors, with a clock of 2.40 G Hz, interconnected through
an InfiniBand network, equipped with 4x QDR switches.Comment: 9 pages, 9 figures, added reference to final peer reviewed version on
conference paper and DO
Real-time cortical simulations: energy and interconnect scaling on distributed systems
We profile the impact of computation and inter-processor communication on the
energy consumption and on the scaling of cortical simulations approaching the
real-time regime on distributed computing platforms. Also, the speed and energy
consumption of processor architectures typical of standard HPC and embedded
platforms are compared. We demonstrate the importance of the design of
low-latency interconnect for speed and energy consumption. The cost of cortical
simulations is quantified using the Joule per synaptic event metric on both
architectures. Reaching efficient real-time on large scale cortical simulations
is of increasing relevance for both future bio-inspired artificial intelligence
applications and for understanding the cognitive functions of the brain, a
scientific quest that will require to embed large scale simulations into highly
complex virtual or real worlds. This work stands at the crossroads between the
WaveScalES experiment in the Human Brain Project (HBP), which includes the
objective of large scale thalamo-cortical simulations of brain states and their
transitions, and the ExaNeSt and EuroExa projects, that investigate the design
of an ARM-based, low-power High Performance Computing (HPC) architecture with a
dedicated interconnect scalable to million of cores; simulation of deep sleep
Slow Wave Activity (SWA) and Asynchronous aWake (AW) regimes expressed by
thalamo-cortical models are among their benchmarks.Comment: 8 pages, 8 figures, 4 tables, submitted after final publication on
PDP2019 proceedings, corrected final DOI. arXiv admin note: text overlap with
arXiv:1812.04974, arXiv:1804.0344